Static versus dynamic predictions of protective stepping following waist-pull perturbations in young and older adults

The purposes of this study were: (1) to determine the frequency of protective stepping for balance recovery in subjects of different ages and fall-status, and (2) to compare predicted stepping based on a dynamic model (Pai and Patton, 1997. Journal of Biomechanics 30, 347 354) involving displacement and velocity combinations of the center of mass (COM) versus a static model based on displacement alone against experimentally induced stepping. Responses to three different magnitudes of forward waist pulls were recorded for 13 young, 18 older-non-fallers and 18 older-fallers. The COM phase plane trajectories derived from motion analysis were compared with the model-predicted threshold values for stepping. We found that the older fallers had the highest percentage of stepping trials (52%), followed by older-non-fallers (17.3%), and young (2.7%) at the lowest perturbation level. Younger subjects stepped less often than the elderly at the middle level. Everyone consistently stepped at the highest level of perturbation. Overall, the dynamic model showed better predictive capacity (65%) than the static model (5%) for estimating the initiation of stepping. Furthermore, the threshold for step initiation derived from the dynamic model could consistently predict when a step must occur. However, it was limited, especially among older fallers at the low perturbation level, in that it considered some steps 'unnecessary' that were presumably triggered by fear of falling or other factors.     

Cloning, sequencing, and recombinant expression of the porcine inhibitor of carbonic anhydrase: a novel member of the transferrin family

The plasma from many vertebrates contains a component that specifically binds and inhibits carbonic anhydrase II with nanomolar affinity. Amino-terminal sequencing of pICA, the previously identified 79-kDa carbonic anhydrase inhibitor isolated from porcine plasma [Roush, E. D., & Fierke, C. A. (1992) Biochemistry 31, 12536-12542], and sequencing of four proteolytic fragments of pICA revealed that each of the partial sequences has 40-80% sequence identity with members of the transferrin protein family. We describe here the isolation of a full-length cDNA clone of pICA from a lambda gt11 porcine liver cDNA library. Heterologous expression of this cDNA clone in a Pichia pastoris expression system led to the secretion into the medium of 5 mg/L of a 79-kDa protein that specifically reacts with anti-pICA antibodies and binds tightly to a carbonic anhydrase-Sepharose affinity column. Pairwise sequential alignment of pICA with various transferrins reveals an amino acid identity as high as 64% and predicts that 16 transferrin disulfide bonds are conserved. However, despite these structural similarities, the properties of pICA are distinct from the properties of transferrin. pICA exhibits a significantly decreased affinity for iron that can be attributed to the loss of one of the eight amino acids that coordinate iron in the transferrins as well as both of the arginine residues responsible for anion binding. In addition, the antigenic determinants of pICA and the transferrins are not identical. These data imply that pICA, along with saxiphilin, is a member of a diverse superfamily of transferrin-like proteins with functions other than iron binding.     

Antimicrobial drug residues in milk and meat: causes, concerns, prevalence, regulations, tests, and test performance

This paper presents a historical review of antimicrobial use in food animals, the causes of residues in meat and milk, the types of residues found, their regulation in Canada, tests used for their detection, and test performance parameters, with an emphasis on immunoassay techniques. The development of residue detection methods began shortly after the introduction of antimicrobials to food animal production in the late 1940s. From initial technical concerns expressed by the dairy industry to the present public health and international trade implications, there has been an ongoing need for reliable, sensitive, and economical methods for the detection of antimicrobial residues in food animal products such as milk and meat. Initially there were microbial growth inhibition tests, followed by more sensitive and specific methods based on receptor binding, immunochemical, and chromatographic principle. An understanding of basic test performance parameters and their implications is essential when choosing an analytical strategy for residue testing. While each test format has its own attributes, none test will meet all the required analytical needs. Therefore the use of a tiered or integrated system employing assays designated for screening and confirmation is necessary to ensure that foods containing violative residues are not introduced into the food chain.     

Acute endothelium-mediated vasodilation is not impaired at the onset of diabetes

Vascular injury and impaired vascular function are central to the increased mortality associated with diabetes. Hyperglycemia in diabetes has been suggested to play a role in this process, in part by impairing the function of the vascular endothelium. It has been difficult, however, to isolate the direct effect of glucose in both humans and in animal models of diabetes. This was evaluated in the present study in 7 rats that were chronically instrumented with a Transonic flow probe at the iliac bifurcation of the abdominal aorta, a nonoccluding catheter inserted immediately anterior to the flow probe, and a femoral vein catheter. Acute infusions of acetylcholine and sodium nitroprusside (1 and 10 microg/min IA) increased hindquarter blood flow significantly by approximately 27 and 10 mL/min over baseline, respectively, at the high dose. Streptozotocin (70 mg/kg IV) was administered, but normoglycemia was maintained with continuous intravenous insulin infusion to control for potential streptozotocin side effects. Diabetes was induced 5 to 7 days later by stopping the insulin infusion. Hindlimb blood flow (measured 24 hours per day) decreased during the diabetic period and was accompanied by an increase in mean arterial pressure, suggesting a vasoconstrictor response. However, the responses to acetylcholine and sodium nitroprusside were not altered significantly on either day 2 or day 6 of the diabetic period. This suggests that neither endothelium-mediated vasorelaxation nor responsiveness to nitric oxide is impaired during the initial phase of diabetes and that diabetic hyperglycemia does not have a significant, direct effect to impair endothelium-mediated relaxation in insulin-dependent diabetes mellitus. The mechanism for the change in baseline blood flow and its potential influence on endothelial function, however, are not known.     

Decreased cholesterol efflux from fibroblasts of a patient without Tangier disease, but with markedly reduced high density lipoprotein cholesterol levels

A 51-yr-old woman without clinical evidence of Tangier disease, but with an extremely low high density lipoprotein (HDL) cholesterol level, was studied. No defect in the major structural protein of HDL, apolipoprotein AI (apo AI), was detected. A preponderance of small HDL particles in the patient's plasma suggested defective uptake of cellular cholesterol. Efflux of [3H]cholesterol from patient fibroblasts to normal apo AI was decreased 50%. Cholesterol efflux to HDL was also decreased, but efflux to trypsin-modified HDL was not. The patient's cells partitioned more exogenously provided [3H]cholesterol into free cholesterol and synthesized greater amounts of phosphatidylcholine than did normal or Tangier fibroblasts. Her fibroblasts did not differ from normal fibroblasts in sterol synthesis rate, cellular cholesterol and cholesterol ester content, or incorporation of oleate into cholesterol ester. The data indicate the presence of a defect in apolipoprotein-dependent cellular cholesterol efflux that differs from that seen in Tangier disease. These findings are the first evidence that other low HDL cholesterol syndromes, besides Tangier disease, may also be associated with cholesterol efflux abnormalities. The identification of mutant genes responsible for apolipoprotein-mediated efflux abnormalities should provide valuable insights into cellular mechanisms involved in the reverse cholesterol transport pathway.     

Hospitalization for serious blood and skin disorders following use of co-trimoxazole

AIMS: The objective of this study was to quantify the risk of serious blood and skin disorders associated with co-trimoxazole. METHODS: We conducted a population-based cohort study of serious blood and skin disorders requiring hospitalization among otherwise healthy users of co-trimoxazole at Group Health Cooperative and Puget Sound (GHC). RESULTS: During the years 1987 to 1993 we found six cases of co-trimoxazole-associated blood disorders and three cases of co-trimoxazole-associated skin disorders yielding risks of 5.6/100,000 (95% CI 2.6-12.2) and 2.8/100,000 (95% CI 0.9-8.2) respectively. In all cases found there was prompt recovery after discontinuation of co-trimoxazole. We found no cases of toxic epidermal necrolysis. CONCLUSIONS: We conclude that the risk of blood and skin disorders associated with the use of co-trimoxazole leading to hospitalization is low.     

Use of supercritical fluid extraction as a method of cleaning anterior cruciate ligament prostheses: in vitro and in vivo validation

The process of supercritical fluid extraction (SFE) using carbon dioxide as the mobile phase is finding increasing numbers of applications in a wide variety of industries for the extraction, separation, and cleaning of materials. This study assessed the usefulness of this approach in removing surface contaminants from a knitted polyester anterior cruciate ligament (ACL) prosthesis before packaging and sterilizing the product during manufacture. The physical, dimensional, and chemical properties of SFE treated compared with commercially scoured control samples were characterized using a number of textile test methods: electron spectroscopy for chemical analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and solvent extraction analysis. The biocompatibility of the samples was measured in terms of their ability to generate CD18 integrin expression on activated human polymorphonuclear cells, and their inflammatory response when implanted for up to 30 days in the knee joint of rats. SFE treatment was successful in removing most of the nonpolar contaminants from the ACL prosthesis and reducing the amount of residuals to a commercially acceptable level. However, some nitrogen containing compounds and polar salts were not removed by the SFE process. The results from the biocompatibility tests demonstrated that the cleaner SFE treated prosthesis induced significantly lower CD18 expression than the scoured control fabric, and was also associated with a milder inflammatory response and a more rapid rate of healing during the 30 day animal trial. Another effect of SFE processing was to cause the polyester device to shrink and lose porosity because of yarn contraction and modification of the polymer's microcrystalline structure.     

Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes

The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.